手性NACE法测定酒石酸美托洛尔片剂中对映体的含量  

Determination of enantiomers of metoprolol tartrate in tablets by chiral NACE

作　　者：焦亚军 李君 侯序 张帆[1] 王利娟[1] 郭怀忠[1] JIAO Ya-jun;LI Jun;HOU Xu;ZHANG Fan;WANG Li-juan;GUO Huai-zhong(Key Laboratory of Pharmaceutical Quality Control of Hebei Province,College of Pharmaceutical Seiences,Hebei University,Baoding 071002,China)

机构地区：[1]河北省药物质量分析控制重点实验室河北大学药学院,保定071002

出　　处：《药物分析杂志》2019年第1期127-132,共6页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金资助项目(21405031);河北省自然科学基金资助项目(B2015201160);河北大学自然科学基金资助项目(2014-06;2014-07);河北大学实验室开放项目(sy201667);河北大学研究生创新资助项目(x201734)

摘　　要：目的:建立手性非水毛细管电泳法(NACE法)测定酒石酸美托洛尔片剂中对映体的含量。方法:以D-葡萄糖酸-硼酸络合酸为手性选择剂,在优化过的NACE手性分离条件下展开相关研究。优化的NACE手性分离条件:未涂层熔融石英毛细管(55.0 cm×50μm,有效长度为45.0 cm);背景缓冲液为含8 mmol·L-1 D-葡萄糖酸、120 mmol·L^(-1)硼酸、43.2 mmol·L^(-1)三乙胺的甲醇溶液;10 cm,5 s重力进样;运行电压20 kV;检测波长224 nm;柱温为室温。结果:酒石酸美托洛尔的2个对映体质量浓度在7.5～250.0μg·mL^(-1)范围内,与峰面积呈现良好的线性关系;对映体1的定量下限和检测下限分别为7.5μg·mL^(-1)和2.5μg·mL^(-1);对映体2的定量下限和检测下限分别为25.0μg·mL^(-1)和7.5μg·mL^(-1);对映体1和对映体2的加样回收率分别为99.7%、98.0%、97.2%和97.7%、98.0%、98.0%,均在95.0%～105.0%范围内。6个批次的酒石酸美托洛尔片剂中对映体1和对映体2的标示量百分含量均在96.6%～102.5%之间。结论:该方法经验证可用于酒石酸美托洛尔片剂中对映体含量的测定。Objective:To establish a method for the determination of enantiomers of metoprolol tartrate in tablets by nonaqueous capillary electrophoresis(NACE).Methods:D-Gluconic acid-boric acid complex was used as the chiral selector.The experiments were carried out under the optimized chiral NACE conditions.The optimized conditions were as follows:Enantiomeric sepraration was performed in an unmodified fused silica capillary of 50.0 μm with 55.0 cm of total length and 45.0 cm of effective length;the running buffer solution was a mixture of 8 mmol·L^-1 D-gluconic acid,120 mmol·L^-1 boric acid and 43.2 mmol·L-1 triethylamine in methanol;injection were performed hydrostatically for 5 s at a 10 cm height difference;the applied voltage was 20 kV;the detection wavelength was 224 nm;the experiments were performed at room temperature.Results:Good linearity for the two enantiomers of metoprolol tartrate were obtained in the range of 7.5-250.0 μg·mL^-1.The limit of quantification(LOQ)and the limit of detection(LOD)for enantiomer 1 were 7.5 μg·mL^-1 and 2.5 μg·mL^-1,respectively,and for enantiomer 2,25.0 μg·mL^-1 and 7.5 μg·mL^-1,respectively. The recoveries for each enantiomer were 99.7%,98.0%,97.2% and 97.7%,98.0%,98.0%,respectively,with all in the range of 95.0%-105.0%.The contents of enantiomer 1 and enantiomer 2 in six batches of metoprolol tartrate tablets were all in the ranges of 96.6%-102.5%.Conclusion:The method validated by methodology is suitable for the determination of enantiomer contents in metoprolol tartrate tablets.

关 键 词：D-葡萄糖酸-硼酸络合酸 酒石酸美托洛尔片剂 手性对映体 含量测定 非水毛细管电泳 

分 类 号：R917[医药卫生—药物分析学]